Cancer chemotherapy initially relied on agents with broad cytotoxicity. As greater understanding of the cancer cell biology was gained, targeted therapies were developed that inhibited the activity of signaling proteins, often kinases, involved in the regulation of vital cellular functions and uniquely or excessively expressed in cancer cells. Compounds with activity solely against a particular target enzyme were generally sought in developing such drugs, although as more of the kinome became experimentally accessible, it became clear that many of these drugs had activity against additional kinases. Differences in effectiveness but also general toxicity could often be attributed to these additional inhibitory activities. Additionally, cancers often develop resistance to such targeted therapies and in relatively short periods of time. Thus, there exists a need for further and more effective drugs.